Description: This is the almost true story of Lorenzo Odone, his parents, and their fight against a terrible disease, adrenoleukodystrophy (ALD). The tale begins in 1984 when Lorenzo, then age 5, is diagnosed with the disease. The doctors give him a prognosis of relentlessly increasing disability and death within two years. There is no treatment. The Odones do not accept this verdict and embark on a dramatic search for a way to save their son.

Benefits of the Movie: "Lorenzo's Oil" is an enthralling medical detective story. It can serve as a motivator in the study of the scientific method, chemistry, biology, neurology, and genetics. The film is an excellent introduction to the medical research establishment and the ethics of clinical trials.

Merely watching this movie is a hard-hitting life experience. It teaches courage, persistence and that sometimes motivated people can achieve what had seemed impossible. It also shows that the disabled are real people with feelings and intelligence. The film explores some of the problems in getting society to take note of and to address extremely rare diseases.

The movie and this Learning Guide provide several opportunities to teach critical viewing skills.

The movie contains a key factual error that provides an excellent opportunity to teach the scientific method. At the time the movie was released, scientific studies had demonstrated that Lorenzo's Oil did not work for other ALD patients who, like Lorenzo, had already developed symptoms of the disease. Lorenzo's reaction to the Oil was an anomaly. (We are not aware of any explanation for why the Oil worked with Lorenzo.) The worries of the scientists and ALD Foundation leaders about holding out false hope to families (concerns that were ridiculed in the movie) turned out to be entirely justified. Then, in a twist of fate, scientific studies completed ten years after the film was made found Lorenzo's Oil to be effective in preventing ALD in a different group of people, boys with the ALD genetic defect who did not yet have neurological symptoms. Ironically, these studies were performed by Dr. Hugo Moser. In the movie, the character modeled on Dr. Moser, Dr. Nikolais, is portrayed as the epitome of the unresponsive medical establishment. TWM's Lesson Plan -- The Development of Lorenzo's Oil, Strange Twists of Fate, and the Scientific Method uses these circumstances as the basis for an exercise in applying the scientific method and developing hypotheses in a real world situation.

QUICK DISCUSSION QUESTION: How many resources should society devote to finding cures for rare diseases such as ALD?

Suggested Response: There is no one right answer to this question. Perhaps the strongest argument is that money should be spent on the illnesses that affect the most people and for which there is the highest chance of finding a cure. However, that is very difficult for people who have a rare disease and their families to accept.

How Soap Cleans -- illustrating several different types of atomic and intermolecular bonding -- Middle School/Jr. High and High School Chemistry;

Possible Problems:SERIOUS. There are heartrending scenes showing Lorenzo's increasing disability and his coughing fits in which, unable to swallow, he chokes on his own saliva. The film may upset sensitive children. It may be a good idea to tell children as they watch this movie that it is a mostly true story, that Lorenzo, in the end, survives, although he is still seriously disabled, and that the Odones' efforts to save their son have allowed other children affected by the disease to live happy and productive lives.

Some viewers may be distracted by Nick Nolte's heavily accented English. However, Nolte simply provides a fair rendition of how the real Augusto Odone sounds when he speaks English. See Roger Ebert's Review of this film for the Chicago Sun-Times.

Parenting Points: For children not strongly interested in science review with them the key factual error described in the Benefits section. Then ask and help your child to answer the Quick Discussion Question. To the extent that you can, immediately after the movie, or at odd times over the next week (for example at the dinner table or in the car on the way to school) talk to them about the genetics of the transmission of ALD, why women don't get the disease but carry the gene, the difference between X and Y chromosomes, dominant and recessive genes, etc. See Lesson Plan: Predicting Combinations for Alleles in a Zygote Using Punnett Squares.

If you have a child who is interested in science review the entire Helpful Background section with him or her and go through each of the three lesson plans associated with this Learning Guide.

ALD causes the loss of the white fatty insulating covering (myelin sheath) on nerve fibers within the brain. See diagram of neuron showing myelin sheath. The disease also causes the progressive degeneration of the adrenal gland. Its basis is genetic. The ALD genetic defect is very rare, with a minimum incidence of one in every 16,800 births. ALD affects all races equally.

Very long chain saturated fatty acids, VLCSFAs (see Diagrams of Four Fatty Acids), are normally found in blood plasma and other tissues of the body. In patients with ALD, VLCSFAs are not broken down by the body. These fatty acids accumulate in the brain and in the adrenal glands. By an unknown mechanism, perhaps an autoimmune response, this causes inflammation and the loss of myelin. (The name of the disease comes from "adreno" relating to the adrenal gland; "leuko" referring to the white color of the healthy myelin sheath; and "dystrophy" which means abnormal development.) Several other rare inherited disorders are also characterized by the loss of myelin. Multiple sclerosis is an example of an acquired disease which can destroy myelin.

Diet is one source of VLCSFAs. The body also makes its own VLCSFAs. Enzymes in the smooth endoplasmic reticulum add hydrocarbon units (H-C-H) to the chains of shorter fatty acids. (The endoplasmic reticulum is a highly convoluted membrane within cells which makes proteins and lipids. Lipids are molecules that do not dissolve in water, such as fats. In the movie, Augusto Odone used paper clips a model for links in the hydrocarbon chain.)

In normal individuals, VLCSFAs are kept at safe levels by peroxisomes in the liver which oxidize excess VLCSFAs. ALD is caused by a defect in a gene which prevents the body from making the enzyme that transports VLCSFAs to the peroxisomes. (Peroxisomes are organelles within cells that, among other things, contain enzymes that break down various lipids.)

ALD affects only males. It is caused by a defect in a recessive gene on the X chromosome. (See Lesson Plan - Predicting Combinations for Alleles in a Zygote Using Punnett Squares.) Symptoms appear in boys between the ages of 4 and 8 and may include behavioral changes such as poor memory, loss of emotional control, and dementia. Other symptoms are muscle weakness, difficulty in walking, spasticity, as well as deficiencies in vision, hearing, and speech. Progression of the disease brings deteriorating muscle tone, difficulty in swallowing and, eventualy onset of coma. The disease results in progressive paralysis, hearing loss, blindness, vegetative state, and death.

It is now possible to determine if the defective gene is present in boys before the onset of symptoms and in females who are carriers for the genetic defect. This provides the opportunity for therapies at a time when they are most effective and for disease prevention through genetic counseling. Lorenzo's Oil has a preventive effect in boys who are less than 6 years old, do not have neurological symptoms, and who have a normal MRI (magnetic resonance imaging scan) of the brain. It is strongly recommended for this group. Adrenal steroid replacement therapy is mandatory for the 70% of ALD patients who have adrenal insufficiency. Bone marrow transplants help boys and adolescents with early brain involvement, however, risk of mortality and morbidity is high for this treatment. Bone marrow transplants are not recommended when symptoms are already severe. Symptomatic and supportive treatments for ALD include physical therapy, psychological support, and special education. As of 2005, researchers believe that the inflammatory/autoimmune process is the best avenue for finding a cure for the disease. New methods of immunosuppression are under active investigation.

The prognosis for ALD, which affects approximately 35% of children with the defective gene, is poor. Death usually occurs one to ten years after symptoms appear. Because ALD is so rare, the availability of public and private funding for research is limited.

The Development of Lorenzo's Oil and the Scientific Method: Modifying a Hypothesis Based On the Results of an Experiment

The movie traces the steps in discovering Lorenzo's Oil. It can be used to show the scientific method in operation.

The scientific method is the process by which scientists find answers to questions about the physical world. The physical sciences such as physics and chemistry usually use experimentation. Other sciences such as biology or anthropology may also use observation and description. In this Learning Guide we will discuss experimentation.

Science recognizes that what actually happens in nature is the only measure of scientific truth. In science: "phenomena is king."

The scientific method has four steps:

research that explores the current knowledge on the subjects to be investigated;

setting out assumptions and stating a hypothesis; the latter is an educated guess based on the research (hypotheses must be described in terms that can be tested experimentally);

designing and conducting the experiment; and

reaching a conclusion.

The scientific method can also be summarized as developing a hypothesis (steps 1 and 2) and then testing it through experimentation or observation (step 3). Based on the experiment the hypothesis will be tentatively accepted as true or shown to be false (step 4). The hypothesis may be modified based on the results of the experiment and additional research.

A hypothesis is a tentative explanation of a fact or situation in the natural world which can be tested through experiments or observation. A scientific hypothesis is not really proven true or correct. It can be rejected because it is determined to be inconsistent with the data. If experiments or observations are consistent with the hypothesis (for example if the predictions that logically flow from the hypothesis turn out to be true) then the hypothesis will be regarded as being "provisionally" true. It will be kept as a working hypothesis until new evidence either finds it to be faulty or until many experiments over a long period of time confirm it. But even then, the hypothesis is always subject to revision if new data, such as new or more accurate tests, are developed.

A basic assumption of all science is that changes in physical phenomena have a cause which, after careful research and experimentation, may be determined. The best hypotheses are stated in terms of a cause and a resulting effect. For example, oil and water will separate when put together. They will not combine. However, if you add an emulsifier (such as soap) and stir it in, the oil and water will combine into one liquid. (A liquid in which two compounds combine, such as oil and water, is called an emulsion.) The hypothesis would be stated as follows: "Soap added to oil and water in a container will cause the oil and water to combine into an emulsion." The control for this experiment is that instead of adding a certain amount of soap, you add that same amount of oil and water in the same proportion as in the original sample. For an explanation of how soap works on oil and water, see How Soap Cleans.

In designing experiments to test a hypothesis, the factor which you change or which you introduce is called the "independent variable." (In our example, the independent variable is the soap.) The change occurs in what is called the "dependent variable." In our case, the dependent variable is the oil/water mixture which, after we add the soap, changes into an emulsion. To put it another way, the independent variable is the one the scientist changes to see what the result will be. The dependent variable is what changes in response. In designing experiments, we want to have only one independent variable so that we know that this variable has caused the change in the dependent variable.

Very few hypotheses can be stated without assumptions. An assumption is really a hypothesis that the researcher feels comfortable in making. Scientists discourage assumptions. They are required to be based upon facts and stated in the design of any experiment.

A model seeks to explain a natural phenomenon or process in graphic terms. Models are useful when they help scientists develop new hypotheses. In the case of Lorenzo's Oil, the model of the sink with two taps and a clogged drain helped scientists and the Odones think about what had to be done to lower the level of VLCSFAs in the bodies of children with ALD. Another model is the idea that atoms have valence shells that have a certain number of electrons in them and which need a certain number of electrons to be stable or "happy."

A scientific theory is a group of related hypotheses which have been confirmed through repeated experiments or observation and which provide a coherent explanation for a large number of natural phenomena. Theories are internally consistent, have survived repeated tests, and are helpful in problem solving. Examples include, Newton's "clockwork" universe, the cell theory (that bodies of complex organisms are made up of cells), plate tectonics theory, and the theory of biological evolution through natural selection.

On occasion, a scientific theory will be discarded or modified. This occurs when new observations cannot be explained by the theory. Scientists will then try to come up with a new theory that takes account of all of the provisionally confirmed hypotheses and the new data. An example, is what happened to Newton's clockwork universe. These hypotheses, Newtons three laws of motion and the law of universal gravitation, were first enunciated in 1687. They were shown by repeated experiments to accurately predict natural phenomena. They came to be accepted as laws of the natural world. However, as science progressed there were some new observations that didn't seem to gibe with Newton's laws. In 1915, Albert Einstein showed that his theory of relativity fit more closely to the facts especially at speeds that approached the speed of light. While Newton's laws of motion had been repeatedly confirmed in experiments and are still adequate for speeds that do not approach the speed of light, Einstein's theories describe motion in areas in which some of Newton's laws fail.

The key to the evaluation of a hypothesis is whether it will predict or describe events in the real world. No matter how much we might cherish the hypothesis, if it doesn't consistently predict phenomena it must be revised or rejected outright. For this reason, the scientific method requires that the researcher be rigorously honest in reporting the results of his experiments, even if those results contradict his long held beliefs.

APPLYING THE SCIENTIFIC METHOD TO THE DEVELOPMENT OF LORENZO'S OIL
THE STORY OF A THERAPY THAT WORKS ... BUT NOT FOR THE PEOPLE FOR WHOM IT WAS DESIGNED

There are two additional points about Lorenzo's Oil. First, it doesn't treat the cause of the disease, which is the body's failure to make a protein necessary to transport VLCSFAs to the peroxisomes in the liver. It lowers the concentration of VLCSFAs by reducing the rate at which they are formed. (In the model of the sink with two taps and a clogged drain, Lorenzo's Oil closes the biosynthesis tap. A cure for ALD would open the drain by allowing the body to take the VLCSFAs to the peroxisomes.) Lorenzo and all ALD patients continue to be unable to metabolize VLCSFAs even when treated with Lorenzo's Oil. Second, there are side effects to taking the oil. For example, Lorenzo's Oil reduces platelet count (thromboytopaenia). The side effects, however, are not nearly as damaging as the disease.

The Adult Forms of ALD

About 65% of boys born with the defective ALD gene do not develop the childhood cerebral disease that is called ALD. Most remain unaffected until adulthood, most developing adrenomyelonueropathy (AMN) between the ages of 21 and 35. AMN is a milder form of ALD that affects the long tracts of the spinal cord but does not develop into the cerebral inflammatory disease. People with AMN can survive into their 80s. Symptoms include: leg stiffness, difficulty with walking due to spasticity, urinary disturbances, impotence, cognitive defects, emotional disturbances and depression. Neurological disability occurs slowly over several decades, which differs from the rapid deterioration that occurs in the cerebral inflammatory form of the disease. About 5% of teenagers or adults develop the inflammatory cerebral disease. About half of the women who are carriers of the disease exhibit mild neurological symptoms in their later years. These symptoms include a partial paralysis of the legs, moderate sensory loss, urinary problems, and peripheral neuropathy. Scientists don't know why some children get ALD while some adults get AMN.

"Competitive inhibition of enzymes", the chemical process which is the basis for the benefits of Lorenzo's Oil, is also referred to in the science fiction novel Flowers for Algernon. This chemical process played a role in the sequence of events that caused damage to Charly Gordon's brain. See Learning Guide to "Charly".

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Ethics in Medical Research

Why were the doctors so conservative and unwilling to take risks?

One of the main principals of the medical profession is to do no harm. This means that physicians should not interfere in the normal processes of the body unless they know that their intervention will be beneficial. There are two basic reasons for this doctrine. First, the body in many cases will heal itself. Second, the history of science and the work of every scientist abounds with examples of hypotheses that made a lot of sense but which didn't work when tested. Many treatments that were once relied upon by medical science have turned out to be harmful rather than helpful. (Remember bleeding people to relieve the "humors" in their blood?) Many drugs or medical devices, once thought to be safe, have been withdrawn from the market after causing death or injury. Examples are IUDs, thalidomide and Vioxx. It is for this reason that federal law, administered by the Food and Drug Administration, requires that a medicine be both safe and effective before it can be prescribed by physicians or sold to the public.

Another reason that the doctors could not participate with the Odones in trying Lorenzo's Oil on their son was that the Odones had not complied with any of the codes of ethics that related to testing drugs on human beings. The first code of ethics for physicians conducting research on human subjects arose out of the Nuremberg War Crimes Trials. Nazi doctors had performed inhumane and often deadly experiments on thousands of concentration camp prisoners. Examples included: injection of live viruses into the blood stream; injection of foreign substances such as gasoline; immersion in ice water; and forced ingestion of poisons. Seven physicians were sentenced to death and another 16 were given prison sentences. (For a movie about the trials of judges and lawyers who participated in Nazi war crimes, see Judgment at Nuremberg.) In their verdict against the doctors, the Nuremberg Judges set out the first comprehensive code governing medical research on human subjects. It is called the The Nuremberg Code.

Abuses of subjects in clinical trials have not been confined to Nazi Germany. In the U.S., black men involved in a study of the effects of syphilis were denied effective therapies for decades so that scientists could watch the natural course of the disease if it went untreated. In 2005 the U.S. Environmental Protection Agency (EPA) proposed to study the effects of the use of insecticides known to be dangerous to children by giving video cameras and money to families (mostly poor families) who used the insecticides. The parents were to record the effects of insecticide exposure on their children. The plan was only dropped when two U.S. Senators blocked President Bush's nominee to head the EPA and would not permit a vote on the nomination until the proposal for the study was rejected.

Ethics rules relating to clinical trials are strict because a desire for career advancement or financial gain might lead scientists to take unnecessary risks with the lives of patients. Problems in this area are especially acute with drug companies which invest millions in developing new drugs and want to recoup this investment. It is not infrequent that drugs, once thought to be safe, are pulled from the market when more extensive research shows that they have unacceptable side effects. In 2004/2005, the National Institutes of Health was rocked by a scandal when it was disclosed that scientists making recommendations for treatments were also taking consulting fees from the companies which made drugs used in those treatments. (For example, it was reported that two-thirds of the members of a panel that made recommendations that resulted in increased use of certain drugs for high blood pressure were accepting payments the makers of the drugs.)

For the above reasons, scientists are trained not to gamble with human lives. Ethical scientists (the vast majority) will not perform clinical trials on human beings until the procedure has been checked and rechecked and until trials using animals have been successful. Clinical trials use an elaborate procedures to ensure that the subjects of the tests are not being abused: (1) ongoing informed consent; (2) adverse event reporting; (3) ongoing data and safety monitoring; and (4) continuing review by an independent review board. The Odone's experiment with Lorenzo's Oil, necessarily had none of these protections.

The Odones Were Not Doctors and Had No Time

Obviously for the Odones, trying anything was better than just watching while Lorenzo died. In addition, they had no conflict of interest (the ambition for fame or fortune) that might affect the judgment of a scientist. The Odones were aware that many promising treatments (many hypotheses) didn't work out as expected. They knew that giving more long chain fatty acids to a boy who was unable to metabolize some very long chain fats was a risk. They knew about the animal studies in which erucic acid had caused heart disease in rats. (Before trying the erucic acid on Lorenzo, Deirdre (Micheala's sister) took it for a short period. However, the Odones knew that experimentation on one subject is not enough to verify the safety of a therapy, especially when the experiment lasts only for a short period.) The Odones were incredibly lucky to find a therapy on the first or second try that did more good than harm.

The doctors wanted the Odones to passively accept what the doctors had to offer; which was, essentially, nothing. The Odones said that:

We respectfully claimed the right to have an independent mind and to study everything available in the literature, formulate hypotheses and test them. Interestingly enough, they turned out to be true. [The researchers] believe that science has its own pace and they believed it's a bit leisurely. .... Our message to parents is: realize that your interests and the doctors' interests are not parallel. You may have a motivation and a time limit that these people do not have. "Lorenzo's Oil: A Movie Outruns Science" New York Times, Feb 9, 1993, by Gina Kolata.

Why the Doctors Were Hesitant About Lorenzo's Oil After It Had Worked on Lorenzo.

When the oil normalized Lorenzo's VLCSFA level and his condition stopped deteriorating, the Odones wanted Lorenzo's Oil to immediately be made available to every ALD child. The doctors complied with this request. (Dr. Moser said it took only 30 days to get approval for an open clinical study of Lorenzo's Oil.) However, the doctors refused to advocate Lorenzo's Oil as a proven treatment because the Odones' evidence was only anecdotal. Evidence that comes from the experience of one or several individuals and is not based on scientifically designed experiments is called anecdotal. Often anecdotal evidence turns out to be an anomaly or based on some set of facts that are not disclosed. Scientists are taught to be very suspicious of anecdotal evidence.

The doctors' suspicions increased when, in their clinical studies, Lorenzo's Oil failed to stop the progression of the disease. It turned out that Lorenzo's case was an anomaly. Lorenzo's Oil does not consistently work with children who have already developed neurological symptoms. After the film was released, Dr. Moser did a ten year study which showed that the Oil works with most ALD children when it's administered before neurological symptoms develop and when the children have a normal MRI. He was elated to find that Lorenzo's Oil is an effective preventive therapy for ALD. The irony is that, except for Lorenzo himself, Lorenzo's Oil doesn't work for people who have already begun to suffer from symptoms of the disease.

Genetic Counseling For Carriers of the ALD Defective Gene

Genetic counseling informs parents before the wife gets pregnant about the chances of the child having genetic defects. All couples in which the woman is a carrier of the ALD genetic defect should think very carefully about adoption as an alternative to having biological children. Adoptive parents form bonds with their children which are as strong as the bonds of biological parents. There are also programs in which women with no known genetic defects agree, for a fee, to be artificially inseminated. The child is then adopted by the wife of the father and raised as the couple's own. Males with the ALD gene who live into adulthood will not have male children who have the disease (unless they marry a carrier) but all of their female children will at least be carriers. If the mother is also a carrier (and the father has the ALD genetic defect), 50% of the daughters will be females with ALD. (This is Punnett Square #4 in the Lesson Plan entitled Predicting Combinations for Alleles in a Zygote Using Punnett Squares.) Adoption is an excellent alternative for people with the defective ALD genetic defect.

The Myelin Project the non-profit foundation started by the Odones will send teachers an excellent lesson plan for high school level students. It is especially strong in the area of medical ethics. Call them at 800-869-3546.

The use of the movie "Lorenzo's Oil" as a Teaching Tool
by Bradley J. Smith, Ph.D., Biology Department, University of Colorado at Denver; this is for college level biology students and as of May, 2005, was slightly outdated in its description of the current state of knowledge about ALD;

The third important storyline links Lorenzo to the crucified Christ who suffered for the salvation of others. (This could also be referred to as a symbol that runs through the film and has several aspects.) Clustered at the beginning of the movie are scenes of the Odones praying in church. Religious sounding music is also played in many parts of the movie. The image of Lorenzo and his mother is contrasted with a an image of the Madonna and Child. "Many of the scenes of Easter mass are shot from high above, focusing first on the priest and his acolytes; then, moving in closer, on the heads of Michaela and Augusto Odone, bowed in prayer ... Later in the film, similar high-overhead shots are used to show Michaela and Augusto, never again at mass but often, in turn, as they are doing research in the library of the National Institutes of Health in Bethesda, a secular cathedral to science ...." Late in the film there is a scene which brings the religious imagery into focus when Augusto Odone says to his wife, "Do you ever think that maybe all this trouble has been for somebody else's kid?" The film closes on this theme with images of a church ceiling showing frescoes of angels and cameo shots of several young boys with ALD attesting to their well-being due to Lorenzo's Oil. " Medicine and the Movies: Lorenzo'Oil at Century's End Anne Hudson Jones, Ph.D., quotation beginning with "Many of the scenes ..." has been taken from this article.

A fourth, actually a set of storylines, are the subplots relating to the family members and friends who help the Odones. There are true aspects to many of these. Omouri really did come from Africa to help his friend Lorenzo. Deirdre came to help and submitted herself as a guinea pig. Don Suddaby, the chemist in England really existed (and played himself in the movie). We don't know how much the filmmakers kept to the literal truth in the subplots about the other friends, the workers in the chemical factory, and the librarian, but certainly these ring true. From the standpoint of critical viewing, it is important to note that these subplots are all used in a way that enriches and enhances the emotional power of the movie.

The linkage of the Odones' story to various archetypical storylines create a "richer, far more complex text than a medical or journalistic account of Lorenzo's case would give." Ibid.

As a compliment to the religious imagery and the symbol of Lorenzo as the Christ, the film makes a strong statement that prayer alone will not bring relief to Lorenzo. The early religious scenes of the film give way to similarly shot scenes in the library. Religious music accompanies these scenes and other important moments, such as when Michaela finds the article on oleic acid in a Polish scientific journal and in the scene after the partial success of the Oil and the Odones, just before the testimonials when the camera pans to a ceiling of a church adorned with frescoes of angels.
One analyst asserted that the film relies on three false myths of American culture. The first is that a cure can be found to any illness if only the bureaucracy and red tape will get out of the way. People want desperately to believe this. The second is a strong belief that perseverance, hard work and love can conquer any ailment. Third, is the theme that mainstream science is indifferent to the suffering of patients and their families. See comments of Dr. Arthur Caplan, then director of the Center for Biotechnics at the University of Minnesota, quoted in "Lorenzo's Oil: A Movie Outruns Science" New York Times, Feb 9, 1993, by Gina Kolata.

The imagery, music, lighting, and camera work in this movie are very direct in helping to build the emotion of each scene. We have already noted the music of the religious oriented scenes and the library scenes. There are at least two scenes in which the music is contrasted with a scene of normal life giving us a sense of great foreboding: (1) the scene of the party just before Lorenzo falls from his bike; and (2) Lorenzo's birthday party. In the scenes before the Odones receive the diagnosis, the camera sweeps through the family home and the neighborhood creating an imminent sense of danger. The same is true of the lighting, and while these techniques might appear heavy handed in other films, most audiences will accept them in this movie because the horror shown by the music, camera work, and lighting are more than matched by the horror of the Odones' situation.

In a few scenes in the film, the language used by the actors is Italian with English subtitles. Most of these scenes are very emotional. Putting the words in a beautiful foreign language with the translation in text on the screen insulates us from these emotions and, at the same time makes the scenes more poignant. They also make the scenes more memorable. We know that Mr. Odone is speaking from the depths of his heart when he lapses into Italian.

Truth and Fiction in "Lorenzo's Oil"

The description of the disease and the path of the Odones in inventing Lorenzo's Oil are correctly laid out. Lorenzo was a bright boy who could speak several languages. His family had spent several years in the Comoros Islands. Augusto Odone (whose accent Nick Nolte imitated) worked for the World Bank and Michaela Odone was a linguist. The characterizations of the personalities of Michaela and Augusto Odone, Deirdre, and Dr. Nikolais, appear to be reasonably accurate, at times exaggerated for dramatic effect. (Michaela's "mother tiger" qualities were overstated. She didn't slap her husband or kick her sister Deirdre out of the house. Note that Michaela felt that these scenes were within the limits of poetic license and did not object. "Troubled Waters for 'Lorenzo's Oil'", Baltimore Sun, 1993: 26 Jan. D1, 3.) Lorenzo developed ALD, was treated at Johns Hopkins and in Boston, etc. Mrs. Odone's sister, Deirdre was a carrier for the ALD gene but did not have children at this time. She came to help the Odones and submitted to tests to see if the preparation of erucic acid would be harmful and if it would reduce levels of VLCSFAs in her blood. The side plots of with Omouri and Don Suddaby are primarily based on fact.

Much of what is not factually accurate rings true in the literary sense. For example, Lorenzo did not participate in the clinical trial of a diet free of VLCSFAs. That study was completed before Lorenzo was diagnosed with ALD. However, this was an important study and having Lorenzo participate allowed the study and the issues surrounding it to be presented in the film.

Lorenzo was started on the Boston immunosuppression as quickly as possible. The rapidly progressive brain disease has inflammatory and autoimmune components. Immunosuppression was, and still is, conceptually the best approach because dietary therapy effects take months to show themselves. Email from Dr. Hugo Moser, April 27, 2005.

What appears to be one major flaw are the scenes in which the second child of Wendy Gimble, who had already started to exhibit neurological symptoms of ALD, got better when given Lorenzo's Oil. The fact that the oil stopped the progression of the disease in Lorenzo was an anomaly which scientists could not duplicate in other children who already had developed neurological symptoms.

The film was not without its critics, chief among them Dr. Moser (Dr. Nikolais in the movie.) First and most importantly, Dr. Moser noted that clinical follow-up studies at the time the movie was made indicated that Lorenzo's Oil was not nearly as effective as portrayed in the film. He pointed to the irresponsibility of the movie makers when, without checking with the specialists in ALD, they claimed that Lorenzo's Oil worked on children who had already begun to develop symptoms. The boys who gave testimonials at the end of the movie could very well have been among the 65% of boys with the defective gene who don't develop symptoms until later in life. (Note that the clinical studies that led Dr. Moser to doubt the effectiveness of Lorenzo's Oil included children whose disease had already begun to manifest itself. Dr. Moser, a careful scientist, always noted that "The crucial question as to whether timely administration of Lorenzo's Oil to asymptomatic boys with the biochemical defect of ALD can prevent the onset of neurological disability is still under investigation." It was only in 2002, almost ten years after the movie was released, that a study was completed that definitively proved that Lorenzo's Oil was very beneficial if treatment began before symptoms appeared. Dr. Moser ran the study. If it had turned out that Lorenzo's Oil did not work consistently for any population, the film would be much less relevant today and would be a classic example of Hollywood irresponsibility. Many people got very lucky on this one.)

Dr. Moser's second objection was that "[t]he movie tends to exaggerate the conceptual contributions that the Odones have made. The conceptual framework for the use of the monounsaturated oils, in particular oleic acid, stems from the work of Dr. William Rizzo. [footnote omitted] The Odones clearly deserve credit for arranging the manufacture of the glyceryl trioleate oil [oleic acid]. The most significant credit relates to their predicting that the use of glyceryl trierucate [erucic acid] would have a more powerful effect, for achieving its manufacture, and for testing it immediately in their own family." Quotations in the last two paragraphs from "Suspended Judgment: Reactions to the Motion Picture 'Lorenzo's Oil'", Hugo W. Moser, M.D., Controlled Clinical Trials 15:161-164 (1994). (See also "Lorenzo's Oil: A Movie Outruns Science" New York Times, Feb 9, 1993, by Gina Kolata.)

Mr. Odone's claims are consistent with Dr. Moser's account of his family's contribution to the development of Lorenzo's Oil.

In October [1984] we organized an international symposium. One of the doctors said that giving patients oleic acid might reduce levels of the very long chain fatty acids. The reasoning, though I didn't know it at the time, was that such a substance might block the enzymes that synthesize very long chain fatty acids in the body.... I looked at animal experiments done over the past 50 years with different oils and decided to add a second ingredient called erucic acid. [If you give Lorenzo's Oil to rats or mice their hearts clog up and they die.] That is where the dispute started. The dogma was that erucic acid was dangerous in people. "Lessons from Lorenzo", Augusto Odone interviewed by David Concar, New Scientist, January 26, 2002.

A third objection voiced by Dr. Moser is that the movie implied a "conflict between objective therapeutic trials and the immediate needs of the patients. Such a conflict did not exist here .... The therapy was and is available to all families who wish to participate in the trials and virtually all do so...." Moser in "Suspended Judgment: Reactions to the Motion Picture 'Lorenzo's Oil'", citation above. He noted that approval of the open clinical trial took only 30 days. "Lorenzo's Oil" Film Review in The Lancet Vol. 341: Feb 27,1993 Mr. Odone agrees that Dr. Moser was not accurately portrayed in the film, saying: "The movie was a little bit unfair to him.... He knows ALD inside and out, and he's a very compassionate person.... Dr. Moser always kept his mind open." "Lorenzo's Oil Brings Hope for the Afflicted", by Rita Rubin, USA TODAY, October 21, 2002; See also "Lessons from Lorenzo", cited above.

Dr. Moser's fourth important criticism referred to the "inaccurate and mean spirited representation of the parents' organization [the United Leukodystrophy Foundation]. The scene in which parents demand access to Lorenzo's Oil over the objections of the organization is not only preposterous, it simply did not occur. ... Contrary to the film's presentation, the organization has had an important role in making the oil available to patients. The organization has also supported research ..." "Lorenzo's Oil" Film Review in The Lancet Vol. 341: Feb 27,1993. (Dr. Moser also noted that "except that he wears a bow tie, [Peter Ustinov] has copied my appearance and speech with remarkable accuracy." "Lorenzo's Oil" Film Review in The Lancet Vol. 341: Feb 27, 1993.)

Each of Dr. Moser's criticisms raise important concerns. As to Dr. Moser's third and fourth points, every film needs human villains. They are difficult to find in situations such as the fight against ALD when everyone is trying to do the right thing and there are many competing interests involved. "Lorenzo's Oil", on the whole, handles this conflict well. While Dr. Moser is unfairly treated, the audience cannot fail to see that he does what he can within the ethical restrictions of his profession. The characters of the Muscatines (the leaders of the parents' group) are allowed to state their case, and it is a powerful argument.

Some Events in the Lives of the Odones After the Film

After Lorenzo's condition stabilized, the Odones established a non-profit foundation, The Myelin Project. The goals of the Myelin Project are to find ways to remyelinate nerves. However, because of the Odones' experience with the medical research establishment, the Myelin Project doesn't simply give money to scientists and expect them to come up with a cure.

Behind the Myelin Project is a multinational gathering of families struck by one demyelinating disease or another. Refusing to accept the conventional view that science cannot be hurried, they resolved to advance the moment when myelin could be restored. They have done this by creating a framework in which researchers can cooperate effectively, by giving scientists adequate, prompt financing and by continuously interacting with them. ... To counter researchers' endemic conservative stance, we at The Myelin Project constantly remind them of two aphorisms: "fortune favors the brave," and "you never know until you try." The Myelin Project: An Overview.

In June, 2000, Michaela Odone died of lung cancer at the age of 60. Mr. Odone said that the constant care his wife provided to Lorenzo took a toll on her health. "It was her sacrifice for Lorenzo. She was with him 16 hours a day, continuously. We did not go out. We did not entertain people. We did not take vacations. It wore her out." (Los Angeles Times, June 12, 2000, page B4). See Remembering Michaela Augusto Odone's paean to his late wife.

Lorenzo lived until he was 30 years old, dying on May 30, 2008. Until his death, his mind was active and he communicated by blinking his eyelids to say no and moving his fingers to say yes. He enjoyed music and being read to. Lorenzo never regained his sight, his speech, the ability to eat, the use of his arms, the use of his hands (other than tiny wiggles of his fingers), or the use of his legs. When Lorenzo died his father and his life-long friend Oumouri Hassane were at his side. He is survived by his father Augusto, his brother Francesco and his sister Cristina.

2. Focus on a single link in the hydrocarbon tail of a VLCSFA. What are the elements that make up that link and how many atoms of each element are contained in each link?

3. What does the term VLCUFA stand for and how is it different than a VLCSFA? Draw a diagram showing the different linkages.

4. What two parts of the body are most damaged by ALD?

5. What are the two sources of VLCSFAs in the body?

6. Name and describe the part of the cell in which VLCSFAs are synthesized by the body.

7. What are peroxisomes and what is their role in maintaining safe levels of VLCSFAs in normal people?

8. What do normal people have that ALD patients lack?

9. Describe the model that Augusto Odone developed to show the problem of reducing VLCSFAs in Lorenzo's body.

10. What was the contribution of the article by the Polish chemists and where did it leave the Odones?

11. Explain how Lorenzo's Oil works to prevent the buildup of VLCSFAs in the body.

12. In the movie, the Odones were confronted with a number of questions that they had to answer. An early question was why Lorenzo's VLCSFA levels went up even when the VLCSFAs were eliminated from his diet. Hopefully, by looking at the sink model you know the answer. (It is that VLCSFAs were still being made by biosynthesis.) Another question the Odones had to answer was why biosynthesis of saturated fats was reduced when Lorenzo was given oleic acid, an unsaturated fat. Why did that occur?

13. Does Lorenzo's Oil correct the damage done by VLCSFA's?

14. When do symptoms of ALD appear and how many boys with the defective ALD gene will actually get the disease and show symptoms during that period?

15. Name five symptoms of ALD.

16. What is the prognosis for patients with untreated ALD?

17. What is the earliest point at which ALD can be diagnosed with modern medical techniques?

18. Name two current treatments for ALD.

19. Are excessive levels of VLCSFAs part of the cause of the deterioration of the myelin sheath in ALD sufferers or is it a mere byproduct of that process? How do we know this?

20. What is adrenomyelonueropathy (AMN), how does it relate to ALD, and who gets it?

21. EXTRA CREDIT: The Odones were very lucky in their effort to find a way to arrest the progress of ALD in their son. One of the reasons that the scientists were reluctant to immediately publish the remarkable drop in the level of VLCSFAs in Lorenzo's blood was that they had no idea of what Lorenzo's Oil would do to the human body. Focus on the different possible effects of competitive inhibition and describe a possible scenario for damage that could have been caused by the ingestion of Lorenzo's Oil.

1. What risks did the Odones take by giving a combination of oleic acid and erucic acid to Lorenzo?

2. What did the Odones do that no ethical scientist would do?

3. What is a clinical trial? Why are there such strict rules regulating clinical trials?

4. What are anecdotal results and why are research doctors suspicious of them? Give an example of an anecdotal result from the movie.

5. Why don't drug companies usually develop drugs for diseases like ALD? Do you fault them for this?

6. What was different about the Odone's situation that justified their willingness to take the risks despite the objections of the physicians?

7. Why is ALD called an "orphan disease"?

8. What is the goal of the Myelin Project, the foundation started by the Odones?

9. Do you think that female carriers of ALD should have children? What about the boys who, because of Lorenzo's Oil and careful medical treatment, survive to adulthood and get married? Should they have children?

10. Do you think that the leaders of the ALD society (Mr. and Mrs. Muscatine) as portrayed in the movie acted in the way that leaders of a support group should act?

QUESTIONS RELATING TO CRITICAL VIEWING SKILLS

1. Describe two scenes in which a sense of foreboding in the music is contrasted with a scene of normal life.

2. Name two archetypal storylines which are used to add depth to the film.

3. Describe two scenes or cinematic effects in which Lorenzo is associated with the Christ child.

4. Name two myths of American culture that are fostered by this film.

5. A few emotional scenes in the film are spoken in Italian, with subtitles. Why did the director use this device?

OTHER DISCUSSION QUESTIONS

1. Think of the theme of the film that relates to man battling a harsh and uncaring natural world. What is ironic about this theme in its application to the experience of Lorenzo and Michaela Odone?

2. Do you think that the Odones were arrogant as the head of the Foundation claimed?

3. What was the role of luck in the Odones' search for a way to stop the deterioration of Lorenzo's condition?

4. What happens when scientists work in isolation and don't communicate with each other?

5. What does this movie demonstrate about the role of scientific symposia in the process of advancing scientific knowledge?

6. What is "modeling" in scientific research and how does it help scientists make new discoveries?

1. Compare the reaction of this family to the other families with children who had the same illness. Could every family have reacted in the way that the Odones did?

2. Were there any special attributes that the Odone family possessed which permitted them to find a way to stop the deterioration of their son's health?

3. Should Michaela have felt guilty that it was her genes that contained the defect that caused Lorenzo to have ALD?

ILLNESS - DISABILITIES

4. Before the discovery of Lorenzo's Oil, was it better to simply allow children with the ALD defect to die?

5. Michaela Odone devoted herself to caring for Lorenzo and gave up most other parts of her life. She exhausted herself in caring for him. Her husband believes that it hastened her death. Do you think that she reacted in the right way to her son's illness? What would you have done?

6. What did you think about Dr. Nikolais? Was he a good doctor or not?

(Do what you are supposed to do; Persevere: keep on trying!; Always do your best; Use self-control; Be self-disciplined; Think before you act -- consider the consequences; Be accountable for your choices)

1. The movie starts with the following passage on the screen:

Life has meaning only in the struggle.
Triumph or defeat is in the hands of the Gods . . .
So let us celebrate the struggle!
-- Swahili Warrior Song.

What are the filmmakers trying to tell us by putting this quote at the beginning of the movie?

2. Is there a difference between fulfilling a responsibility (doing what you are supposed to do, persevering, and always doing your best) and what the Odones did for Lorenzo?

See questions in Illness-Disabilities section above.

CARING

(Be kind; Be compassionate and show you care; Express gratitude; Forgive others; Help people in need)

3. Does everyone need people to help them out at certain times? Where would Lorenzo be without those who cared for him? Where would you be if, in your times of need, people had not helped you out?

Links to the Internet: (Note that all links dated before the release of Dr. Moser's study in late 2002 confirming the efficacy of Lorenzo's Oil as a preventive treatment for asymptomatic boys with the ALD genetic defect will note that Lorenzo's Oil has not been proven to work scientifically.)

A class which is enthusiastic about this film can hold a bake sale or a car wash and donate the proceeds to The Myelin Foundation.

The class can write a letter to Lorenzo, individually or as groups. The teacher can review the letters and send the best to Lorenzo c/o The Myelin Project, 2136 Gallows Road, Suite E, Dunn Loring, Virginia 22027.

TWM grants free limited licenses to copy TWM curriculum materials only to educators in public or non-profit schools and to parents trying to help educate their children. See TWM's Terms of Use for a full description of the free licenses and limits on the rights of others to copy TWM..